Human Papillomavirus Type 11 DNA in Squamous Cell Carcinomas and Pre-existing Multiple Laryngeal Papillomas

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Abstract
The case histories of 4 patients are presented, who developed an invasive squamous cell carcinoma from pre-existing multiple laryngeal papillomatosis (two juvenile-onset and two adult-onset) during a long latency period. A series of 14 routinely processed, paraffin-embedded biopsies obtained from these patients (including both benign papillomas and carcinomas) were analysed using in situ DNA-hybridization technique with 35S-labelled Human papillomavirus (HPV) DNA probes of HPV types 6, 11, 16, 18 and 30. The lesions were also assessed by indirect immunoperoxidase (IP-PAP) technique to demonstrate the expression of HPV structural proteins. On light microscopy, morphology was consistent with HPV infection in all 14 biopsies. HPV antigen expression could not be demonstrated in any of the papillomas or carcinomas, however. HPV 11 DNA was present in high copy numbers in both the benign and malignant lesions of 2 patients, both presenting with the juvenile-onset disease. The present findings provide support for the role of HPV as an etiological agent in laryngeal squamous cell carcinoma, most probably acting synergistically with chemical or physical carcinogens (one patient received irradiation and 2 others were smokers). It seems clear that an infection by the 'low risk' HPV types 6 and 11 by no means excludes the possibility of developing a laryngeal malignancy, so far ascribed to the 'high risk' type HPV 16 only.